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An experimental vaccine appears to give monkeys some protection against a version of HIV, the virus that leads to AIDS. Scientists say the research gives big clues about the most essential elements needed to develop a successful HIV vaccine for humans.

In the study, published today in the journal Nature, scientists gave rhesus monkeys a vaccine against SIV, the monkey version of HIV. The monkeys were then exposed to a strain of the SIV, a difficult-to-treat strain that was different than the one used to create the vaccine. The monkeys that were vaccinated seemed to be partially protected against the virus, which reduced their susceptibility to infection by 80 percent.

When the monkeys did become infected, the amount of the virus that appeared in their blood was substantially lower than monkeys that were not vaccinated.The successful vaccines all contained an essential element, called Env, which helps the virus bind to the antibodies that can destroy it.

“The study demonstrates very clearly that in order to prevent acquisition of the virus, a vaccine needs to have an Env glycoprotein component,” said Eric Hunter, professor of pathology and co-director of the Center for AIDS Research at Atlanta’s Emory University who was not involved with the study. “I would say this is significant progress in the process of trying to develop a protective HIV vaccine.”That a vaccine that was made using one strain of the virus protected the monkeys from a different and difficult strain is also a major advancement, scientists say. Dr. Carl Dieffenbach, director of the division of AIDS for the National Institute of Allergy and Infectious Diseases, the government agency that funded the study, said that’s because there are multiple versions of the HIV virus that attack humans.

“There’s so much variability in the population of viruses that are circulating. When you have viruses that are different, can the immune system use the response it’s made against virus A to mount a successful repulsion of a related virus,” Dieffenbach said. “That’s one of the major things this study did.”

The scientists were testing elements of HIV vaccines that were successful in humans in a 2009 trial. Dieffenbach said their findings now give some idea as to what made those vaccines work.

“We’re trying to bring those human findings full circle, and this gets us about half way around the loop,” Dieffenbach said.

Published: January 4, 2012. US Army Medical Research Institute of Infectious Diseases

Results from a recent study show that novel vaccine combinations can provide partial protection against infection by Simian Immunodeficiency Virus (SIV) in rhesus monkeys. In addition, in the animals that became infected, the optimal vaccine combinations also substantially reduced the amount of virus in the blood. Results from the studies were published online today in the journal Nature.

This proof-of-concept study, which tested MVA, Ad26, and Ad35 vector-based vaccines, is the first to show partial vaccine protection in the stringent animal model involving heterologous, neutralization-resistant SIVmac251 viral challenges in rhesus monkeys. Preclinical studies of vaccine candidates have typically shown post-infection virologic control, however protection against acquisition of infection has previously only been reported using less rigorous viral challenges. The new Ad26/MVA and Ad35/Ad26 vector-based vaccine regimens resulted in over 80% reduction in the per-exposure probability of acquisition of infection against repetitive challenges of SIV, a virus similar to HIV that infects monkeys.

"This study allowed us to evaluate the protective efficacy of several prime-boost vaccine combinations, and these data will help guide the advancement of the most promising candidates into clinical trials," noted lead author Dr. Dan Barouch of Beth Israel Deaconess Medical Center at Harvard Medical School and the Ragon Institute of MGH, MIT, and Harvard.

Further analysis also provided insights into the immune responses that might have provided protection, called "immune correlates." The results show that antibodies to Env (the envelope protein that makes up the outer coat of the virus) correlated with protection against acquisition, whereas both T cell and antibody responses correlated with post-infection virologic control.

"These distinct immunologic correlates likely reflect fundamentally different requirements to block establishment of infection compared with controlling viral replication after infection," said Col. Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research and senior author on the paper.

Barouch noted that "we have clearly shown that including Env in the vaccine is beneficial." The findings also suggest that a substantial degree of protection can be achieved against stringent virus challenges, even in the absence of high levels of tier 2 neutralizing antibodies.

These new preclinical studies provide support for advancing the Ad26/MVA prime-boost vaccine candidate into clinical development. Collaborators are planning clinical testing of this HIV vaccine regimen in healthy adults at research sites in the U.S., East Africa, South Africa, and Thailand.